Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Sweden.
Department of Biosciences, Cardiff University, UK.
J Parkinsons Dis. 2019;9(1):17-29. doi: 10.3233/JPD-181525.
Rats and mice with unilateral damage to the nigrostriatal dopamine system-induced by neurotoxins, such as 6-hydroxydopamine, overexpression of α-synuclein, or injections of toxic synuclein protofibrils-are widely used as experimental models to mimic the loss of dopamine neurons seen in Parkinson's disease. The amphetamine rotation test is commonly used to monitor the extent of motor impairment induced by the lesion, and this test has also become the standard tool to demonstrate transplant-induced functional recovery or the efficacy of neuroprotective interventions aimed to preserve or restore DA neuron function. Although the amphetamine-induced rotation test is highly useful for this purpose it has some important pitfalls and the interpretation of the data may not always be straightforward. Unless the test is applied properly and the data are displayed and interpreted appropriately the conclusions may be misleading or simply totally wrong. The purpose of this review is to draw attention to the potential problems and pitfalls involved in the use of drug-induced rotation tests, and to provide recommendations and advice on how to avoid them.
使用神经毒素(如 6-羟多巴胺)、α-突触核蛋白过表达或有毒的突触核蛋白原纤维注射等方法造成单侧黑质纹状体多巴胺系统损伤的大鼠和小鼠,被广泛用作实验模型来模拟帕金森病中多巴胺神经元的丧失。安非他命旋转测试常用于监测损伤引起的运动障碍程度,该测试也已成为证明移植诱导的功能恢复或旨在保护或恢复 DA 神经元功能的神经保护干预措施的疗效的标准工具。尽管安非他命诱导的旋转测试在这方面非常有用,但它也存在一些重要的缺陷,并且数据的解释并不总是直接的。除非正确应用该测试,并且正确地显示和解释数据,否则结论可能会产生误导,或者完全是错误的。本综述的目的是提请注意在使用药物诱导的旋转测试中涉及的潜在问题和缺陷,并就如何避免这些问题提供建议和指导。